Meloidogyne aegracyperi n. sp. (Nematoda: Meloidogynidae), a root-knot nematode parasitizing yellow and purple nutsedge in New Mexico.

Meloidogyne aegracyperi n. sp. is described from roots of purple nutsedge in southern New Mexico, USA. Mature females are small (310-460 µm), pearly white, with their egg masses completely contained inside root galls. The neck is often at a 90 to 130° angle to the protruding posterior end with the perineal pattern. The distance of the dorsal esophageal gland orifice (DGO) to the base of the stylet is relatively long (4.0-6.1 µm), and the excretory pore is level with the base of the stylet. The anterior portion of the rounded lumen lining of the metacorpus contains 3 to 10 small vesicles. The perineal pattern has a rounded dorsal arch with a tail terminal area that is smooth or marked with rope-like striae. Only two males were found. The body twists 90° throughout its length. The DGO to the base of the stylet is long (3.0-3.3) µm. The cephalic framework of the second-stage juvenile is weak, and the stylet is short (10.1-11.8 µm). The DGO to the base of the stylet is long (3-5 µm). The tail is very long (64-89 µm) and the hyaline portion of the tail is very narrow, making the tail finely pointed. Eggs are typical for the genus and vary in length (85.2-99.8 µm) and width (37.1-48.1 µm), having a L/W ratio of (2.1-2.6). Maximum likelihood phylogenetic analyses of the different molecular loci (partial 18S rRNA, D2-D3 of 28S rRNA, internal transcribed spacer (ITS) rRNA, cytochrome oxidase subunit II (COII)-16S rRNA of mitochondrial DNA gene fragments and partial Hsp90 gene) placed this nematode on an independent branch in between M. graminicola and M. naasi and a cluster of species containing M. chitwoodi. M. fallax, and M. minor. Greenhouse tests showed that yellow and purple nutsedge were the best hosts, but perennial ryegrass, wheat, bentgrass, and barley were also hosts.

Search for a new gauge boson in electron-nucleus fixed-target scattering by the APEX experiment.

We present a search at the Jefferson Laboratory for new forces mediated by sub-GeV vector bosons with weak coupling α' to electrons. Such a particle A' can be produced in electron-nucleus fixed-target scattering and then decay to an e + e- pair, producing a narrow resonance in the QED trident spectrum. Using APEX test run data, we searched in the mass range 175-250 MeV, found no evidence for an A'→ e+ e- reaction, and set an upper limit of α'/α ~/= 10(-6). Our findings demonstrate that fixed-target searches can explore a new, wide, and important range of masses and couplings for sub-GeV forces.

Lack of acute effect of amylin (islet associated polypeptide) on insulin sensitivity during hyperinsulinaemic euglycaemic clamp in humans.

It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeostasis and on insulin sensitivity using the euglycaemic hyperinsulinaemic clamp. The amylin used opposed insulin-mediated glucose disposal in rat soleus muscle at concentrations of 10 nmol/l. Seven subjects were studied on two occasions and infused with either amylin or placebo for 6 h, initially when postabsorptive and then during a euglycaemic hyperinsulinaemic clamp. Mean plasma amylin concentrations during the first 3 h were 2006 +/- 327 pmol/l during amylin infusion and 20 +/- 9 pmol/l during the control infusion. Amylin infusion had no effect on postabsorptive plasma concentrations of insulin (control: 32 +/- 16 vs amylin: 25 +/- 8 pmol/l) or glucose (5.1 +/- 0.1 vs 5.3 +/- 0.1 mmol/l). During the clamp, amylin concentrations were 1636 +/- 422 pmol/l when it was infused and 24 +/- 6 during control infusions. Plasma glucose and insulin concentrations were well matched during the control and amylin infusions (glucose: 4.7 +/- 0.1 vs 4.8 +/- 0.1 mmol/l; insulin: 198 +/- 37 vs 195 +/- 22 pmol/l). Exogenous glucose infusion rates were a mean of 13% lower than control values during the amylin infusion but were not statistically different (p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme immunoassay--a new technique for estimating hemoglobin A1c.

We describe a method for estimating hemoglobin A1c (HbA1c) with a commercially available enzyme immunoassay system. The method is based on microtiter plate technology, utilizing an antibody raised to hemoglobin, the epitope being the Amadori product of glucose plus the first eight amino acids on the N-terminal end of the beta chain of hemoglobin. The enzyme immunoassay displays good within-batch (CV 2.3-2.4%) and between-batch (CV 2.6-5.0%) precision, and the results were not affected by different types of anticoagulant. The method was linear within the expected range of results and showed good correlation (r = 0.88-0.98) with established methods for estimating glycohemoglobin. Using this method, we obtained a reference interval of 2.8-4.9% (central 95%) for HbA1c in a nondiabetic population. The percentages of hemoglobin that were HbA1c in diabetics (6.86% +/- 2.51%) were significantly greater (P < 0.001) than in nondiabetics (3.46% +/- 0.52%).

Von Willebrand factor, plasminogen activator inhibitor-1 and C-reactive protein are markers of thrombolytic efficacy in acute myocardial infarction.

Plasma von Willebrand factor, plasminogen activator inhibitor activity and C-reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t-PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and > or = 50% resolution of maximal ST-deviation on the electrocardiogram. Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism.

Absence of potentiation of the skin response to intradermal bradykinin by a long-acting angiotensin converting enzyme inhibitor, trandolapril, at conventional antihypertensive dosage in human volunteers: a double-blind, randomized, cross-over, placebo-controlled trial.

A double-blind, randomized, cross-over, placebo-controlled study was carried out to determine the extent and duration of potentiation of the action of bradykinin introduced intradermally by a long-acting novel angiotensin converting enzyme (ACE) inhibitor, trandolapril. The investigations were performed in a temperature and humidity-controlled laboratory. Intradermal injections of 1 microgram, 2.5 micrograms and 5 micrograms of bradykinin and normal saline (as control) were made into the forearm skin of eight healthy normotensive male volunteers aged 21-33 years (mean 28 years) at baseline, 2, 4, 8, 24, 48, 72 and 96 hours after either 2 mg trandolapril or placebo given orally. Skin blood flow outside the induced weal was monitored by laser Doppler flowmetry (mean of recordings at four sites adjacent to the weal within the flare area). Flare area and weal volume were also measured. Trandolapril reduced the mean arterial pressure. However, there was no evidence that this activity was associated with a potentiation of the cutaneous action of bradykinin. In conclusion, it would appear that potentiation of the action of bradykinin may not be an important contributing factor to the fall in total peripheral vascular resistance associated with ACE inhibition in humans in the control of hypertension.

Very high concentrations of islet amyloid polypeptide are necessary to alter the insulin response to intravenous glucose in man.

Islet amyloid polypeptide (IAPP) is a beta-cell peptide that can oppose insulin action in animal systems, but has not been shown to have any action in man; previously, we failed to show an effect of infused IAPP on iv glucose tolerance in human volunteers. We have reexamined its effects at even higher concentrations in six volunteers who received iv glucose (0.5 g/kg) during infusions of IAPP (25 and 50 pmol/kg.min) or normal saline. IAPP rose from a mean basal of 14.7 +/- 5.3 pmol/L to peak levels of 1,420 +/- 110, 2,240 +/- 140, and 27.7 +/- 9 pmol/L, respectively. IAPP at 25 pmol/kg.min had no effect on the plasma glucose disposal rate or the total incremental insulin response, but, in contrast, at 50 pmol/kg.min decreased the insulin response to glucose compared to the saline infusion (incremental area under the curve, 11,276 +/- 2,353 vs. 17,549 +/- 2,687 U; mean +/- SEM; P less than 0.02). This decrease was observed both during the first phase (0-10 min postglucose) insulin response (3,210 +/- 985 vs. 4,382 +/- 815 U; P less than 0.05) and the second phase response (11-90 min, 8,520 +/- 1,719 vs. 13,679 +/- 2,326 U; P less than 0.03). Glucose disposal rate, however, was unaffected (2.0 +/- 0.2 vs. 1.9 +/- 0.2). Thus, circulating IAPP concentrations greater than 90 times normal postprandial peaks were necessary to affect the insulin response to glucose. IAPP appears unlikely to be a circulating hormone influencing carbohydrate metabolism in man.

Fetal urine biochemistry: an index of renal maturation and dysfunction.

OBJECTIVE: To construct a reference range for fetal urinary sodium, potassium, urea, creatinine, calcium and phosphate with gestation and to assess to what extent these biochemical indices are modified in fetuses with lower urinary tract obstruction. DESIGN: Prospective descriptive study. SETTING: Royal Postgraduate Medical School London. SUBJECTS: 24 women between 17 and 35 weeks gestation with an ultrasound diagnosis of fetal lower urinary tract obstruction, with or without renal dysplasia and a control group of 26 women between 16 and 33 weeks gestation with normal amniotic fluid volume and fetal anatomy. INTERVENTIONS: Fetal urine samples (1-100 ml) were aspirated from the control fetuses either before termination of pregnancy (n = 9) or at the time of intrauterine transfusion for Rh alloimmunization (n = 17). The fetuses with obstructive uropathy had urine samples aspirated on one occasion (n = 14) or serially (n = 10). MAIN OUTCOME MEASURES: Relation between urine biochemistry and renal damage ascertained clinically or at postmortem. RESULTS: In the control group, urinary sodium and phosphate decreased and creatinine increased significantly with gestational age, consistent with increasing fetal glomerular filtration rate and progressive maturation of tubular function. Urinary sodium and calcium were significantly higher in fetuses with renal dysplasia compared with those with lower urinary tract obstruction but normal renal histology or normal clinical outcome. Serial urinary samples from fetuses with obstructive uropathy showed more pronounced deviation from the normal with increasing gestation in all fetuses with renal dysplasia. The highest sensitivity in the detection of renal dysplasia was shown by urinary calcium (100%) whereas urinary sodium showed the best specificity (80%). CONCLUSION: Renal damage is the direct effect of urinary obstruction, rather than an association so that treatment should start as soon as possible. Urinary biochemistry may be helpful in the management of these patients.

Islet amyloid polypeptide: production by an osteoblast cell line and possible role as a paracrine regulator of osteoclast function in man.

1. The recently discovered peptide islet amyloid polypeptide shows considerable sequence homology with calcitonin-gene-related peptide, itself an alternative product of the calcitonin gene. The possibility that islet amyloid polypeptide might affect calcium homoeostasis and bone cell function was investigated. 2. Islet amyloid polypeptide messenger RNA was found to be expressed by human HTb 96 osteoblast-like cells in culture, and islet amyloid polypeptide immunoreactivity was present in the cell culture medium. 3. Infusion of islet amyloid polypeptide (150 pmol min-1 kg-1) caused a fall in serum calcium and phosphate concentrations in five patients with Paget's disease of the bone. This was similar to that caused by infusion of calcitonin (50 pmol min-1 kg-1). 4. These findings raise the possibility that islet amyloid polypeptide may act as a local factor within bone, produced by osteoblasts and regulating osteoclast function. The possibility of an action of islet amyloid polypeptide on the renal handling of calcium seems unlikely but is not totally excluded.

Continuing controversy in alloimmune thrombocytopenia: fetal hyperimmunoglobulinemia fails to prevent thrombocytopenia.

Two patients with severe alloimmune thrombocytopenia were managed by weekly intrauterine platelet transfusions at 25 to 36 weeks. In one patient high-dose immunoglobulin was also administered weekly to the mother, and high maternal and fetal immunoglobulin levels were achieved. Fetal platelet counts were similar in both patients. The only variable that affected fetal platelet concentration was the posttransfusion platelet count from the previous transfusion.

Preliminary report: role of peptide YY in defence against diarrhoea.

To investigate whether peptide YY (PYY) has a role in minimising fluid loss during diarrhoea, its effect on hypersecretion induced by vasoactive intestinal peptide (VIP) was studied in seven subjects with ileostomies. An isotonic electrolyte solution containing polyethylene glycol 4000 was infused directly into the duodenum and the effluent was collected for 40 min (baseline), then VIP was infused intravenously at 5 pmol.kg-1.min-1 for 500 min. PYY was infused intravenously at low doses (0.4 and 0.2 pmol.kg-1.min-1) for 100 min each during the continuous VIP infusion. Small-intestinal secretion was assessed by effluent weight and by polyethylene glycol dilution, which gave similar results. Plateau ileal output was 501 (SEM 33) ml/h during VIP infusion. PYY caused significant falls in secretion--to 404 (48) ml/h for the lower dose and to 323 (75) ml/h for the higher. It also prolonged small-bowel transit. These findings suggest that PYY is a natural inhibitor of diarrhoea and that its therapeutic potential merits investigation.

Patterns of serum alkaline phosphatase activity in unilateral hepatic duct obstruction: a clinical and experimental study.

The levels of serum alkaline phosphatase (ALP) were measured in eight patients with bile duct obstruction limited to one lobe of the liver. Although an initial rise of enzyme concentration was documented in every patient, unrelieved biliary obstruction was associated with a gradual return of ALP to normal values. The return to normal levels coincided with the development of atrophy of that part of the liver deprived of its bile drainage. An animal model of experimental selective biliary obstruction supported a causative association between reduction of hepatocyte mass and a decrease in ALP activity. It appears that normal serum ALP levels can be expected with advanced obstructive biliary disease. Suspected lobar or segmental duct obstruction warrants investigation--even if liver function tests are normal.

Failure to establish islet amyloid polypeptide (amylin) as a circulating beta cell inhibiting hormone in man.

The presence of islet amyloid polypeptide in amyloid within pancreatic islet cells in Type 2 (non-insulin-dependent) diabetes, and its reported inhibition of glucose uptake by skeletal muscle in vitro, has prompted speculation concerning its role in the pathogenesis of diabetes. We investigated the effect of infused synthetic amidated human islet amyloid polypeptide (mol. wt. 3904, confirmed by mass spectroscopy) on intravenous glucose tolerance. Seven healthy, non-obese volunteers (age +/- SD, 27 +/- 4 years) were infused over 50 min with normal (0.9%) saline or islet amyloid polypeptide at 50 pmol.kg-1.min-1. After 20 min, a bolus of 0.5 g/kg glucose was given within 1 min and blood sampling continued for up to 60 min. Circulating concentrations of islet amyloid polypeptide reached at steady state were 1130 +/- 90 pmol/l. The calculated half-life was 11.8 +/- 0.9 min, metabolic clearance rate 5.7 +/- 0.6 ml.kg-1.min-1 and apparent distribution space therefore 94 +/- 12 ml/kg. However, islet amyloid polypeptide was found to have no effect on the peak value reached, or the total area under the curve for plasma glucose, insulin or glucagon following intravenous glucose. This study suggests circulating islet amyloid polypeptide may not be an important influence on intravenous glucose tolerance in man.

Effects of preprovasoactive intestinal polypeptide-derived peptides on ileal output.

Tumors associated with the Verner Morrison syndrome secrete peptide histidine methionine, its C-terminally extended variant peptide histidine valine, and vasoactive intestinal peptide. There is evidence that vasoactive intestinal peptide mediates diarrhea, but recent evidence suggested that peptide histidine methionine and peptide histidine valine may be at least as important. Infusion of vasoactive intestinal peptide, peptide histidine methionine, and peptide histidine valine into patients with ileostomies produced mean plateau plasma levels of 163, 1301, and 2106 pM, respectively, which are within the range seen in the Verner Morrison syndrome. Vasoactive intestinal peptide produced an integrated ileal output of 174 (53) g (mean [SEM]), compared with only 20 (7) g with peptide histidine methionine and 10 (3) g with peptide histidine valine. These results suggest that vasoactive intestinal peptide is substantially more important than peptide histidine methionine or peptide histidine valine in mediating diarrhea in the Verner Morrison syndrome.

Effects of circulating endogenous catecholamines on plasma glucose, potassium and magnesium.

1. To examine the metabolic effects of increases in circulating endogenous plasma catecholamines, we measured plasma glucose, potassium and magnesium in 14 patients undergoing elective coronary artery bypass grafting. The patients were randomized into two groups and received either sodium nitroprusside (a direct-acting vasodilator) or trimetaphan camsylate (a ganglion-blocking agent) for routine control of blood pressure during the operation. 2. There were significant differences between the two groups in the levels of all three metabolic variables studied. Plasma glucose levels rose in both groups, but were significantly higher in the sodium nitroprusside group [peak levels 9.14 (SEM 0.72)mmol/l compared with 6.71 (0.88) mmol/l, P less than 0.001, analysis of variance]. The cardioplegia solution caused a large increase in plasma magnesium in both groups but in the sodium nitroprusside group the level rose higher [to 1.59 (0.12)mmol/l compared with 1.34 (0.06)mmol/l] and fell faster (P less than 0.05, analysis of variance). In the group receiving sodium nitroprusside, plasma potassium fell, by a mean of 0.34mmol/l, as plasma catecholamine levels rose; no such fall was seen in the group receiving trimetaphan camsylate (P less than 0.05, analysis of variance). 3. It is concluded that the sympathoadrenal system is important in causing metabolic changes during cardiopulmonary bypass and may be relevant in other conditions such as acute myocardial infarction.

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

1. Effects of a single intravenous dose of aspirin (600 mg) on bradykinin-stimulated prostaglandin (PG) and on thromboxane (TX) biosynthesis were determined in nine healthy male volunteers. Plasma concentrations of 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin. TXB2 was measured in serum from blood allowed to clot at 37 degrees C. 2. Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose. Serum TXB2 remained low, whereas PG synthesis recovered within 6 h. 3. Effects of intravenous sodium salicylate (600 mg) were studied identically in eight subjects. Prostanoid biosynthesis was not inhibited. 4. Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1 alpha and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and, on a separate occasion, of vehicle. 5. Aspirin infusion reduced urinary excretion of both metabolites greater than 90%, but excretion of 2,3-dinor-6-oxo-PGF1 alpha recovered more rapidly than did that of 2,3-dinor-TXB2. 6. We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions.

Reflex sympathetic dystrophy (algoneurodystrophy): temperature studies in the upper limb.

The temperature response of the hands to mild cold stress (20 degrees C for one minute) has been measured in 20 normal subjects, 20 patients with reflex sympathetic dystrophy (RSD) and 10 patients with chronic upper limb pain (CULP) of uncertain origin. The results of RSD and CULP groups were significantly (p less than 0.05) different from normal but were indistinguishable. For each patient, 11 variables obtained from the thermal stress test were compared with the normal range. Ten of the RSD group and seven of the CULP group had four or more abnormal variables and were considered to have a thermoregulatory abnormality. The thermal stress test is useful in the objective assessment of RSD. It is non-invasive, patient acceptable and reproducible.

In vivo and in vitro effects of amylin and amylin-amide on calcium metabolism in the rat and rabbit.

Amylin is a new member of the calcitonin/CGRP family: it is a 37 amino acid polypeptide which was recently isolated from amyloid deposits in pancreatic islets obtained from type II diabetics. In the present study we investigated the effect of amylin and amylin-amide on calcium metabolism in the rat and rabbit. Two main methods were used: in vivo hypocalcaemic activity was assessed by measuring plasma calcium levels after injection of the peptide in 50 g rats; and in vitro resorption of cortical bone by disaggregated rat osteoclasts was quantified by scanning electron microscopy together with image analysis. We demonstrate that amylin and amylin-amide have calcitonin-like effects: both are powerful inhibitors of osteoclastic resorption and as a consequence lower plasma calcium in both rats and rabbits. We speculate that the peptide may exert systemic or local regulatory effects on bone cells.

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE: To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud's phenomenon associated with systemic sclerosis. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Dermatology outpatient clinic. PATIENTS: Twenty three patients with Raynaud's phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS: Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT: Reduction in number, duration, and severity of attacks of Raynaud's phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS: Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud's phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION: Both iloprost and nifedipine are beneficial in the treatment of Raynaud's phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.